Peripheral microangiopathy in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study

Abstract

Background: Although pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity.

Methods: Α prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test).

Results: Both IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 μm and 15.8 ± 1.9 μm vs. 11.5 ± 2.3 μm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001).

Conclusion: The findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

Keywords: Chronic thromboembolic pulmonary hypertension; Idiopathic pulmonary hypertension; Nailfold video-capillaroscopy; Peripheral microangiopathy; Precapillary pulmonary hypertension.

Fig. 1

Nailfold video-capillaroscopic features in our study population. a Healthy control; normal capillary density (10 loops/mm), hairpin-shaped capillaries with normal loop width. b Idiopathic pulmonary arterial hypertension (IPAH); moderately reduced capillary density (5 capillary loops/mm), avascular areas (asterisk) and irregularly enlarged capillaries (> 20 μm and < 50 μm, black arrows). c Persistent chronic thromboembolic pulmonary hypertension (CTEPH) post pulmonary endarterectomy; mildly reduced capillary density (7 capillary loops/mm), avascular area (asterisk), abnormal capillary shapes (yellow arrows) and irregularly enlarged capillaries (> 20 μm and < 50 μm, black arrow). Grid pattern represents area of 1mm². Magnification × 200

Fig. 2

Capillary density. Error bars represent the mean capillary density ± standard deviation (SD) in healthy controls (9.7 ± 0.81 loops/mm), patients with idiopathic pulmonary arterial hypertension (IPAH) (8.4 ± 1.2 loops/mm) and patients with chronic thromboembolic pulmonary hypertension (CTEPH) (8.0 ± 1.2 loops/mm). Difference in capillary density was significant among the three groups (p < 0.001). In detail, patients with IPAH presented significantly lower capillary density compared to healthy controls (*p < 0.01). In addition, patients with CTEPH presented significantly lower capillary density compared to healthy controls (**p < 0.001). No difference in capillary density was found between IPAH and CTEPH patients

Fig. 3

Loop width. Error bars represent the mean loop width ± standard deviation (SD) in healthy controls (11.5 ± 2.3 μm), patients with idiopathic pulmonary arterial hypertension (IPAH) (15.7 ± 3.9 μm) and patients with chronic thromboembolic pulmonary hypertension (CTEPH) (15.8 ± 1.9 μm). Difference in loop width was significant among the three groups (p < 0.001). In detail, patients with IPAH presented significantly increased loop width compared to healthy controls (*p < 0.001). In addition, patients with CTEPH presented increased loop width compared to healthy controls (**p < 0.001)